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https://www.readbyqxmd.com/read/29765528/metabolic-changes-associated-with-metformin-potentiates-bcl-2-inhibitor-venetoclax-and-cdk9-inhibitor-bay1143572-and-reduces-viability-of-lymphoma-cells
#1
Vineela Chukkapalli, Leo I Gordon, Parameswaran Venugopal, Jeffrey A Borgia, Reem Karmali
Metformin exerts direct anti-tumor effects by activating AMP-activated protein kinase (AMPK), a major sensor of cellular metabolism in cancer cells. This, in turn, inhibits pro-survival mTOR signaling. Metformin has also been shown to disrupt complex 1 of the mitochondrial electron transport chain. Here, we explored the lymphoma specific anti-tumor effects of metformin using Daudi (Burkitt), SUDHL-4 (germinal center diffuse large B-cell lymphoma; GC DLBCL), Jeko-1 (Mantle-cell lymphoma; MCL) and KPUM-UH1 (double hit DLBCL) cell lines...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29728793/metformin-protects-against-spinal-cord-injury-by-regulating-autophagy-via-the-mtor-signaling-pathway
#2
Yue Guo, Fang Wang, Haopeng Li, Hui Liang, Yuhuan Li, Zhengchao Gao, Xijing He
Spinal cord injury (SCI) is a serious central trauma, leading to severe dysfunction of motor and sensory systems. Secondary injuries, such as apoptosis and cell autophagy, significantly impact the motor function recovery process. Metformin is a widely used oral anti-diabetic agent for type 2 diabetes in the world. It has been demonstrated to promote autophagy and inhibit apoptosis in the nervous system. However, its role in recovery following SCI is still unknown. In this study, we determined that motor function, assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor assessment scale, was significantly higher in rats treated with metformin following injury...
May 4, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29705631/metabolic-switching-in-the-hypoglycemic-and-antitumor-effects-of-metformin-on-high-glucose-induced-hepg2-cells
#3
Yan Lv, Na Tian, Junsong Wang, Minghua Yang, Lingyi Kong
Metformin, a widely prescribed drug for the management of type 2 diabetes mellitus, has potential anticancer effect. Diabetes patients regularly taking metformin have been reported with decreased cancer risk and improved cancer prognosis in recent years. A cell model of high glucose induced HepG2 cells was conducted to mimic insulin resistance, and a 1 H NMR-based metabolomics approach in conjunction with molecular biology was performed to investigate the metabolic changes of high glucose induced HepG2 cells in response to different doses of metformin treatment and to study the differences and links between hypoglycemic and antitumor effects of metformin...
April 21, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29662316/metformin-inhibits-proliferation-and-cytotoxicity-and-induces-apoptosis-via-ampk-pathway-in-cd19-chimeric-antigen-receptor-modified-t-cells
#4
Qian Mu, Miao Jiang, Yuzhu Zhang, Fei Wu, Hui Li, Wen Zhang, Fang Wang, Jiang Liu, Liang Li, Dongshan Wang, Wenjuan Wang, Shiwu Li, Haibo Song, Dongqi Tang
Background: CD19-chimericantigen receptor (CAR) modified T cells (CD19-CAR T cells) have been well documented to possess potent anti-tumor properties against CD19-expressingleukemia cells. As a traditional medicine, metformin has been widely used to treat type II diabetes mellitus and more recently has become a candidate for the treatment of cancer. However, no report has revealed the direct effect of metformin on CD19-CAR T cell biological function and its underling mechanisms. Purpose: The purpose of this research was to explore the effect of metformin on CD19-CAR T cell biological function and the mechanisms involved...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29656591/amp-activated-protein-kinase-dependent-induction-of-autophagy-by-erythropoietin-protects-against-spinal-cord-injury-in-rats
#5
Peng Wang, Zhong-Dong Xie, Chang-Nan Xie, Chao-Wei Lin, Ji-Li Wang, Li-Na Xuan, Chun-Wu Zhang, Yu Wang, Zhi-Hui Huang, Hong-Lin Teng
AIMS: Autophagy has been regarded as a promising therapeutic target for spinal cord injury (SCI). Erythropoietin (EPO) has been demonstrated to exhibit neuroprotective effects in the central nervous system (CNS); however, the molecular mechanisms of its protection against SCI remain unknown. This study aims to investigate whether the neuroprotective effects of EPO on SCI are mediated by autophagy via AMP-activated protein kinase (AMPK) signaling pathways. METHODS: Functional assessment and Nissl staining were used to investigate the effects of EPO on SCI...
April 15, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29576625/targeting-glutaminolysis-in-chondrosarcoma-in-context-of-the-idh1-2-mutation
#6
Elisabeth F P Peterse, Bertine Niessen, Ruben D Addie, Yvonne de Jong, Arjen H G Cleven, Alwine B Kruisselbrink, Brendy E W M van den Akker, Remco J Molenaar, Anne-Marie Cleton-Jansen, Judith V M G Bovée
INTRODUCTION: Chondrosarcoma is a malignant cartilage-forming bone tumour in which mutations in IDH1 and IDH2 frequently occur. Previous studies suggest an increased dependency on glutaminolysis in IDH1/2 mutant cells, which resulted in clinical trials with the drugs CB-839, metformin and chloroquine. In this study, the preclinical rationale for using these drugs as a treatment for chondrosarcoma was evaluated. METHODS: Expression of glutaminase was determined in 120 cartilage tumours by immunohistochemistry...
March 26, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29554968/metformin-induces-autophagy-and-g0-g1-phase-cell-cycle-arrest-in-myeloma-by-targeting-the-ampk-mtorc1-and-mtorc2-pathways
#7
Yan Wang, Wenbin Xu, Zixun Yan, Weili Zhao, Jianqing Mi, Junmin Li, Hua Yan
BACKGROUND: Metformin is a commonly used drug for the treatment of diabetes. Accumulating evidence suggests that it exerts anti-tumor effects in many cancers, including multiple myeloma (MM); however, the underlying molecular mechanisms have not been clearly elucidated. METHODS: The anti-myeloma effects of metformin were evaluated using human MM cell lines (RPMI8226 and U266) in vitro and in vivo NOD-SCID murine xenograft MM model. Cell viability was assessed with CCK8 and cell proliferation was measured by EdU incorporation assay...
March 20, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29531801/inhibition-of-the-mid1-protein-complex-a-novel-approach-targeting-app-protein-synthesis
#8
Frank Matthes, Moritz M Hettich, Judith Schilling, Diana Flores-Dominguez, Nelli Blank, Thomas Wiglenda, Alexander Buntru, Hanna Wolf, Stephanie Weber, Ina Vorberg, Alina Dagane, Gunnar Dittmar, Erich Wanker, Dan Ehninger, Sybille Krauss
Alzheimer's disease (AD) is characterized by two neuropathological hallmarks: senile plaques, which are composed of amyloid-β (Aβ) peptides, and neurofibrillary tangles, which are composed of hyperphosphorylated tau protein. Aβ peptides are derived from sequential proteolytic cleavage of the amyloid precursor protein (APP). In this study, we identified a so far unknown mode of regulation of APP protein synthesis involving the MID1 protein complex: MID1 binds to and regulates the translation of APP mRNA...
December 2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29486734/the-association-of-diabetes-mellitus-and-insulin-treatment-with-expression-of-insulin-related-proteins-in-breast-tumors
#9
Heleen K Bronsveld, Marie L De Bruin, Jelle Wesseling, Joyce Sanders, Ingrid Hofland, Vibeke Jensen, Marloes T Bazelier, Bas Ter Braak, Anthonius de Boer, Peter Vestergaard, Marjanka K Schmidt
BACKGROUND: The insulin receptor (INSR) and the insulin growth factor 1 receptor (IGF1R) play important roles in the etiology of both diabetes mellitus and breast cancer. We aimed to evaluate the expression of hormone and insulin-related proteins within or related to the PI3K and MAPK pathway in breast tumors of women with or without diabetes mellitus, treated with or without insulin (analogues). METHODS: Immunohistochemistry was performed on tumor tissue of 312 women with invasive breast cancer, with or without pre-existing diabetes mellitus, diagnosed in 2000-2010, who were randomly selected from a Danish breast cancer cohort...
February 27, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29482945/metformin-influences-drug-sensitivity-in-pancreatic-cancer-cells
#10
Saverio Candido, Stephen L Abrams, Linda Steelman, Kvin Lertpiriyapong, Alberto M Martelli, Lucio Cocco, Stefano Ratti, Matilde Y Follo, Ramiro M Murata, Pedro L Rosalen, Paolo Lombardi, Giuseppe Montalto, Melchiorre Cervello, Agnieszka Gizak, Dariusz Rakus, Pann-Gill Suh, Massimo Libra, James A McCubrey
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, highly metastatic malignancy and accounts for 85% of pancreatic cancers. PDAC patients have poor prognosis with a five-year survival of only 5-10% after diagnosis and treatment. Pancreatic cancer has been associated with type II diabetes as the frequency of recently diagnosed diabetics that develop pancreatic cancer within a 10-year period of initial diagnosis of diabetes in increased in comparison to non-diabetic patients. Metformin is a very frequently prescribed drug used to treat type II diabetes...
February 12, 2018: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29467947/metformin-inhibits-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-like-process-and-stem-like-properties-in-gbm-via-akt-mtor-zeb1-pathway
#11
Yang Song, Yong Chen, Yunqian Li, Xiaoyan Lyu, Jiayue Cui, Ye Cheng, Liyan Zhao, Gang Zhao
Glioblastoma (GBM) is the most frequent and aggressive brain tumor in adults. In spite of advances in diagnosis and therapy, the prognosis is still relatively poor. The invasive property of GBM is the major cause of death in patients. Epithelial-to-mesenchymal transition-like process (EMT-like process) is considered to play an important role in the invasive property. Metformin has been reported as a regulator of EMT-like process. In this study, we confirmed that metformin inhibited TGF-β1-induced EMT-like process and EMT-associated migration and invasion in LN18 and U87 GBM cells...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29467552/metformin-attenuates-motility-contraction-and-fibrogenic-response-of-hepatic-stellate-cells-in-vivo-and-in-vitro-by-activating-amp-activated-protein-kinase
#12
Zhen Li, Qian Ding, Li-Ping Ling, Ying Wu, Dong-Xiao Meng, Xiao Li, Chun-Qing Zhang
AIM: To investigate the effect of metformin on activated hepatic stellate cells (HSCs) and the possible signaling pathways involved. METHODS: A fibrotic mouse model was generated by intraperitoneal injection of carbon tetrachloride (CCl4 ) and subsequent treatment with or without metformin. The level of fibrosis was detected by hematoxylin-eosin staining, Sirius Red staining, and immunohistochemistry. The HSC cell line LX-2 was used for in vitro studies. The effect of metformin on cell proliferation (CCK8 assay), motility (scratch test and Transwell assay), contraction (collagen gel contraction assay), extracellular matrix (ECM) secretion (Western blot), and angiogenesis (ELISA and tube formation assay) was investigated...
February 21, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29434877/metformin-synergizes-with-rapamycin-to-inhibit-the-growth-of-pancreatic-cancer-in-vitro-and-in-vivo
#13
Jia-Wei Zhang, Fan Zhao, Qing Sun
Previous studies have suggested that metformin may improve the survival rate of patients with pancreatic cancer (PC) by regulating the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway. Rapamycin specifically targets mTOR. In the present study, the efficacy of metformin and rapamycin in isolation and combination were investigated for the treatment of PC. The efficacy of metformin and rapamycin in reducing the proliferation of PC cell line SW1990 in vitro and in vivo was evaluated...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29422962/metformin-and-cancer-an-existing-drug-for-cancer-prevention-and-therapy
#14
Fuming Zi, Huapu Zi, Yi Li, Jingsong He, Qingzhi Shi, Zhen Cai
Metformin is a standard clinical drug used to treat type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome. Recently, epidemiological studies and meta-analyses have revealed that patients with T2DM have a lower incidence of tumor development than healthy controls and that patients diagnosed with cancer have a lower risk of mortality when treated with metformin, demonstrating an association between metformin and tumorigenesis. In vivo and in vitro studies have revealed that metformin has a direct antitumor effect, which may depress tumor proliferation and induce the apoptosis, autophagy and cell cycle arrest of tumor cells...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29396233/in-vivo-evaluation-of-the-synergic-effect-of-metformin-and-mtor-inhibitors-on-the-endothelial-healing-of-drug-eluting-stents-in-diabetic-patients
#15
Héctor Cubero-Gallego, Rafael Romaguera, Josep Gómez-Lara, Joan A Gómez-Hospital, Manel Sabaté, Eduardo Pinar, Montserrat Gracida, Gerard Roura, José L Ferreiro, Luis Teruel, Cristian Tebé-Codorni, Pilar Jiménez-Quevedo, Eduard Montanya, Fernando Alfonso, Ángel Cequier
INTRODUCTION AND OBJECTIVES: Recent animal studies have shown metformin (MF) to impair endothelialization of drug-eluting stents (DES). The aim of this study was to evaluate the effect of MF on the healing of DES in human coronary arteries of patients with diabetes mellitus by optical coherence tomography (OCT). METHODS: The RESERVOIR trial randomized 116 lesions in 112 patients with diabetes mellitus to amphilimus- or everolimus-eluting stents and included mandatory OCT at 9 months of follow-up...
January 25, 2018: Revista Española de Cardiología
https://www.readbyqxmd.com/read/29385181/simvastatin-and-metformin-inhibit-cell-growth-in-hepatitis-c-virus-infected-cells-via-mtor-increasing-pten-and-autophagy
#16
José A Del Campo, Marta García-Valdecasas, Antonio Gil-Gómez, Ángela Rojas, Paloma Gallego, Javier Ampuero, Rocío Gallego-Durán, Helena Pastor, Lourdes Grande, Francisco J Padillo, Jordi Muntané, Manuel Romero-Gómez
Hepatitis C virus (HCV) infection has been related to increased risk of development of hepatocellular carcinoma (HCC) while metformin (M) and statins treatment seemed to protect against HCC development. In this work, we aim to identify the mechanisms by which metformin and simvastatin (S) could protect from liver cancer. Huh7.5 cells were infected with HCV particles and treated with M+S. Human primary hepatocytes were treated with M+S. Treatment with both drugs inhibited Huh7.5 cell growth and HCV infection...
2018: PloS One
https://www.readbyqxmd.com/read/29342230/metformin-as-an-anti-cancer-agent-actions-and-mechanisms-targeting-cancer-stem-cells
#17
Nipun Saini, Xiaohe Yang
Metformin, a first line medication for type II diabetes, initially entered the spotlight as a promising anti-cancer agent due to epidemiologic reports that found reduced cancer risk and improved clinical outcomes in diabetic patients taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Recently, the anti-cancer potential of metformin has gained increasing interest due to its inhibitory effects on cancer stem cells (CSCs), which are associated with tumor metastasis, drug resistance, and relapse...
October 7, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29340030/increased-efficacy-of-metformin-corresponds-to-differential-metabolic-effects-in-the-ovarian-tumors-from-obese-versus-lean-mice
#18
Jianjun Han, Weiya Z Wysham, Yan Zhong, Hui Guo, Lu Zhang, Kim M Malloy, Hallum K Dickens, Gene Huh, Douglas Lee, Liza Makowski, Chunxiao Zhou, Victoria L Bae-Jump
Obesity is a significant risk factor for ovarian cancer (OC) and associated with worse outcomes for this disease. We assessed the anti-tumorigenic effects of metformin in human OC cell lines and a genetically engineered mouse model of high grade serous OC under obese and lean conditions. Metformin potently inhibited growth in a dose-dependent manner in all four human OC cell lines through AMPK/mTOR pathways. Treatment with metformin resulted in G1 arrest, induction of apoptosis, reduction of invasion and decreased hTERT expression...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29323154/effects-of-metformin-on-colorectal-cancer-stem-cells-depend-on-alterations-in-glutamine-metabolism
#19
Jae Hyun Kim, Kyoung Jin Lee, Yoojeong Seo, Ji-Hee Kwon, Jae Pil Yoon, Jo Yeon Kang, Hyun Jung Lee, Soo Jung Park, Sung Pil Hong, Jae Hee Cheon, Won Ho Kim, Tae Ii Kim
Metformin has been known to suppress cancer stem cells (CSCs) in some cancers. However, the differential effects of metformin on CSCs and their mechanisms have not been reported. Herein, metformin induced pAMPK activation and pS6 suppression in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620) cells. The oxygen consumption rate was higher in HT29 cells than in SW620 cells and showed a prominent decrease after metformin treatment in HT29 cells. In glutamine-depleted medium, but not in low-glucose medium, SW620 cells became sensitive to the CSC-suppressing effect of metformin...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29285837/new-metformin-derivative-hl156a-prevents-oral-cancer-progression-by-inhibiting-the-insulin-like-growth-factor-akt-mammalian-target-of-rapamycin-pathways
#20
Thuy Giang Lam, Yun Soo Jeong, Soo-A Kim, Sang-Gun Ahn
Metformin is a biguanide widely prescribed as an antidiabetic drug for type 2 diabetes mellitus patients. The purpose of the present study was to observe the effects of the new metformin derivative, HL156A, on human oral cancer cell and to investigate its possible mechanisms. It was observed that HL156A significantly decreased FaDu and YD-10B cell viability and colony formation in a dose-dependent way. HL156A also markedly reduced wound closure and migration of FaDu and YD-10B cells. We observed that HL156A decreased mitochondrial membrane potential and induced reactive oxygen species (ROS) levels and apoptotic cells with caspase-3 and -9 activation...
March 2018: Cancer Science
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